Heart Patients Warned Against Using Meridia, An Anti-Obesity Drug

By NATASHA SINGER and ANDREW POLLACK

Published: January 23, 2010

European and American drug regulators had two starkly different reactions this week to data on an obesity drug. The raw data from the study indicated that people with certain health problems who took the prescription diet drug Meridia had more heart attacks, strokes and other cardiovascular problems than people getting a placebo.

On Thursday, the European Medicines Agency advised doctors and pharmacists to stop prescribing and dispensing European equivalents of Meridia. The Food and Drug Administration, looking at the same study data on Thursday, took a less forceful step and asked Abbott Laboratories, the maker of Meridia, to put a stronger warning on its label.

The F.D.A. said the new warning should indicate that the drug was not to be used by people who have a history of heart attacks or strokes, or who have uncontrolled high blood pressure.

Abbott, which sells Meridia in Europe under various brand names, including Reductil and Ectiva, indicated Friday that it would comply with the F.D.A.'s labeling request and with the European advisory by suspending sales of the drugs in Europe.

Meridia contains the ingredient sibutramine, which works by increasing neurotransmitter activity in the brain, helping people to feel full after a meal and thereby reducing their food intake. The company said the drug was safe and effective when used in appropriate patients.

''We believe there are many patients who benefit from sibutramine,'' Dr. Eugene Sun, vice president for global pharmaceutical research and development at Abbott, said in a statement.

The company's global sales of sibutramine drugs last year were about $300 million, although usage in the United States has been declining for years.

The study, called the Scout trial, is important for the field of obesity as a whole because its findings contradict what has been the long-held presumption -- that weight-loss drugs are more than just cosmetic. The presumption has been that they will actually help reduce the serious health problems, like heart disease, that are associated with obesity.

The Scout study was the first to actually test this presumption, to see if a diet drug could reduce the risks of heart attacks.

Some experts said the finding that Meridia actually increased such risk in some high-risk patients rather than reduce it could raise questions about the safety of other diet drugs.

The findings might also raise the safety hurdle for new obesity drugs to win approval. However, some experts said the problems might be unique to Meridia, which clearly raises blood pressure and heart rate.

In any case, the significantly different actions by the two health authorities is stirring debate among drug makers and consumer advocates. Did the European agency act too quickly on a set of preliminary data -- or was it moving more forcefully to defend consumer health than its American counterpart?

''The European Medicines Agency has acted appropriately,'' said Dr. Sidney M. Wolfe, the director of the health research group at Public Citizen, a consumer advocacy group in Washington. His group has long asked the F.D.A. to ban Meridia, including a petition last month saying that in the drug's 12 years on the market it has been linked to more than 80 deaths, including 30 people under age 50.

''The F.D.A. has acted recklessly,'' Dr. Wolfe said.

But Dr. Louis J. Aronne, director of the comprehensive weight control program at NewYork-Presbyterian/Weill Cornell Medical Center, said he did not think the drug was unsafe for people who did not already have heart disease. He said he agreed with the F.D.A.'s decision.

''Running up the hill might increase your risk of having a heart attack if you have coronary disease,'' said Dr. Aronne, who is a consultant to various pharmaceutical companies, but not Abbott. ''But if you are 23 years old and have no coronary disease, then running up the hill can prevent you from getting heart disease.''

The European Medicines Agency had requested the study in 2002 because of concerns about side effects like higher blood pressure. The company gave preliminary results from that study to European and American regulators late last year.

The Scout trial was a six-year study involving about 10,000 overweight and obese people who had a history of heart disease or diabetes, or both. About 11.4 percent of those who took the drug had a heart attack, stroke, or died from cardiovascular causes, compared to 10 percent of those getting the placebo, according to data from the study released by the F.D.A.

After reviewing the initial data and questioning Abbott, the European agency said on Thursday that the benefits of sibutramine diet drugs did not outweigh their risks. The suspension of sales is to remain in place, the agency said, unless and until Abbott provided rigorous data identifying a population of people for whom the drug's benefits did outweigh its risks, the agency said.

But Abbott said that the high-risk patients in the study were not the intended audience for the drug. Moreover, the study patients were not asked to take the drug in accordance with its labeling instructions, said Kurt A. Ebenhoch, an Abbott spokesman.

For example, some study patients stayed on the drug for up to six years, Mr. Ebenhoch said, while the drug is approved for one year of use in Europe and for two years in the United States. The label also indicates that patients who do not lose weight on the drug should discontinue using it after six months, but the study patients did not receive such instructions, he said.

Meanwhile, the F.D.A. said it planned to wait for the company's complete report on the study, due in March, before considering further action on the drug. An advisory panel of medical experts is to review the results of the study in a public meeting, most likely in September, an agency spokeswoman wrote in an e-mail message to a reporter. Some obesity experts question the F.D.A.'s decision to leave Meridia on the market for people who do not have cardiovascular disease.

The agency's decision amounts to saying take the drug ''until you get cardiovascular disease,'' said Paul Ernsberger, associate professor of nutrition at the Case Western Reserve University School of Medicine.

But Dr. Ken Fujioka, director of the center for weight management at the Scripps Clinic in San Diego, said he would continue to use the drug if patients were doing well on it, unless the patients felt uncomfortable.

Dr. Fujioka, who is a consultant to some companies developing obesity drugs, said the study data show that the increased risk for heart attacks and other cardiovascular problems was statistically significant only for the subset of patients with both cardiovascular disease and diabetes, ''who nobody would ever give this drug to, anyway.''

Executives at three California companies that hope to win approval of new obesity drugs by next year -- Arena Pharmaceuticals, Orexigen Therapeutics and Vivus -- said Meridia's issues did not apply to them because their drugs did not increase blood pressure.

Timothy E. Morris, chief financial officer of Vivus, said executives were heartened by the F.D.A.'s decision not to take Meridia off the market.